van den Bersselaar Lisa M, Verhagen Judith M A, Bekkers Jos A, Kempers Marlies, Houweling Arjan C, Baars Marieke, Overwater Eline, Hilhorst-Hofstee Yvonne, Barge-Schaapveld Daniela Q C M, Rompen Eline, Krapels Ingrid P C, Dulfer Eelco, Wessels Marja W, Loeys Bart L, Verhagen Hence J M, Maugeri Alessandra, Roos-Hesselink Jolien W, Brüggenwirth Hennie T, van de Laar Ingrid M B H
Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
Genet Med. 2022 Oct;24(10):2112-2122. doi: 10.1016/j.gim.2022.07.009. Epub 2022 Sep 2.
Heterozygous pathogenic/likely pathogenic (P/LP) variants in the ACTA2 gene confer a high risk for thoracic aortic aneurysms and aortic dissections. This retrospective multicenter study elucidates the clinical outcome of ACTA2-related vasculopathies.
Index patients and relatives with a P/LP variant in ACTA2 were included. Data were collected through retrospective review of medical records using a standardized questionnaire.
A total of 49 individuals from 28 families participated in our study. In total, 20 different ACTA2 variants were detected. Aortic events occurred in 65% of the cases (78.6% index patients and 47.6% relatives). Male sex and hypertension emerged as significantly associated with aortic events. Of 20 individuals, 5 had an aortic diameter of <45 mm (1.77 inches) at the time of the type A dissection. Mean age at first aortic event was 49.0 ± 12.4 years. Severe surgical complications for type A and type B dissection occurred in 25% and 16.7% of the cases and in-hospital mortality rates were 9.5% and 0%, respectively.
P/LP ACTA2 variants are associated with an increased risk for an aortic event and age-related penetrance, which emphasizes the importance of early recognition of the disease. Caregivers should be aware of the risk for aortic dissections, even in individuals with aortic diameters within the normal range.
ACTA2基因中的杂合致病性/可能致病性（P/LP）变异会增加胸主动脉瘤和主动脉夹层的风险。这项回顾性多中心研究阐明了ACTA2相关血管病变的临床结局。
纳入携带ACTA2基因P/LP变异的索引患者及其亲属。通过使用标准化问卷回顾病历收集数据。
来自28个家庭的49名个体参与了我们的研究。共检测到20种不同的ACTA2变异。65%的病例发生了主动脉事件（索引患者为78.6%，亲属为47.6%）。男性和高血压与主动脉事件显著相关。在20名个体中，5人在A型夹层时主动脉直径<45毫米（1.77英寸）。首次主动脉事件的平均年龄为49.0±12.4岁。A型和B型夹层的严重手术并发症发生率分别为25%和16.7%，住院死亡率分别为9.5%和0%。
P/LP ACTA2变异与主动脉事件风险增加及年龄相关的外显率有关，这强调了早期识别该疾病的重要性。即使主动脉直径在正常范围内，护理人员也应意识到主动脉夹层的风险。
